Studying Complement Inhibition in Early, Newly Developing Septic Organ Dysfunction

Septic Shock Clinical Trial

— SCIENS  

Official title:

A Phase II Randomized, Placebo-controlled, Double-blind, Dose Controlled Trial in Patients Suffering From Early, Newly Developing Abdominal or Pulmonary Derived Septic Organ Dysfunction to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and to Estimate Efficacy of the New Humanized Monoclonal i.v. Administered Antibody CaCP29

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02246595
• Other study ID #: IFX-1-P2.1
• Secondary ID: 2013-001037-40
• Status: Completed
• Phase: Phase 2
• First received: September 18, 2014
• Last updated: April 22, 2016
• Start date: April 2014
• Est. completion date: December 2015

Study information

• Verified date: April 2016
• Source: InflaRx GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

The trial enrolls patients with early severe sepsis or septic shock displaying at least one newly developed organ dysfunction and showing clinical evidence of pulmonary or abdominal infection. The primary goal of the trial is to assess the pharmacokinetics and pharmacodynamics of the new monoclonal antibody CaCP29 and to characterize safety and tolerability as well as evaluate parameters of efficacy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria at screening:

1. Male or female patients >= 18 years old

2. Written informed consent

3. Occurrence of at least two criteria of a systemic inflammatory response syndrome (SIRS) not explained by other reasons. These criteria should be present within 12 hours prior to screening

4. Suspected or confirmed abdominal or pulmonary infection at screening

5. Broad spectrum i.v. antimicrobial therapy to treat abdominal or pulmonary infection

6. At least one of the following acute organ dysfunctions due to sepsis. Each organ dysfunction must have occurred within 12 hours prior to screening, cannot mainly be explained by other disease processes than sepsis and is judged by the investigator as being caused or directly related to an abdominal or pulmonary infectious focus:

1. respiratory

2. renal

3. hematologic

4. metabolic

5. cardiovascular (occurred within the last three hours)

7. Reasonable likelihood that administration of study drug can be started within 3.5 hours after start of screening process

Key Exclusion Criteria at screening:

1. Sepsis of other primary cause than pulmonary or abdominal source

2. Weight > 130 kg at screening

3. Any other disease and condition that is likely to interfere with evaluation of study product, outcome assessment or satisfactory conduct of the study

4. Patients receiving the following concomitant medication within 14 days prior to screening:

1. Calcineurin inhibitors (e.g., ciclosporine, tacrolimus)

2. Proliferation inhibitors (e.g., everolimus, sirolimus)

3. Anti-metabolites (e.g., mycophenolate, mycophenolic acid, azathioprine)

4. High dose corticosteroids (e.g., > 50mg prednisolon per day or equivalent)

5. Patients receiving high dose immunoglobulins within 3 months prior to screening

6. Patients with following abnormal laboratory result: Neutrocytopenia with neutrophil count < 1,000/mm3 unless likely due to sepsis

7. General criteria:

1. Pregnant (in women of childbearing potential an urine pregnancy test has to be performed) or breast-feeding women

2. Women with childbearing potential (defined as within two years of their last menstruation) not willing to practice appropriate contraceptive measures (e.g., implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy, abstinence) while participating in the trial

3. Participation in any interventional clinical trial within the last three months

4. Prior participation in this clinical trial

5. Patient is chronically bed-bound prior to the onset of sepsis

6. Known intravenous drug abuse

7. Employee at the study site, spouse/partner or relative of any study staff (e.g., investigator, sub-investigators, or study nurse) or relationship to the sponsor

8. No commitment to full aggressive life support (e.g., do not resuscitate order)

Inclusion Criteria at randomisation:

1. At least one of the sepsis related organ dysfunction detected at screening is still present

2. Current treatment with broad spectrum i.v. antibiotics has been started or is ongoing

Exclusion Criteria at randomisation:

1. Time frame between detection of a non cardiovascular organ dysfunction and start of randomization procedure is more than 15 hours

2. Time frame between detection of a cardiovascular organ dysfunction and start of randomization is more than six hours

3. Organ dysfunctions are unlikely to be persistent for next three hours

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Septic Shock
• Severe Sepsis
• Shock, Septic

Intervention

Biological:
• CaCP29

• Placebo

Locations

Country	Name	City	State
Germany	Study Site	Aachen
Germany	Study Site	Augsburg
Germany	Study Site	Bad Saarow
Germany	Study Site	Berlin
Germany	Study Site	Göttingen
Germany	Study Site	Greifswald
Germany	Study Site	Hamburg
Germany	Study Site	Jena
Germany	Study Site	Kiel
Germany	Study Site	Leipzig
Germany	Study Site	Oldenburg

Sponsors (1)

Lead Sponsor	Collaborator
InflaRx GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Concentration of CaCP29	Pharmacokinetic measures include; Plasma concentration over time; Maximum observed concentration per infusion; Concentration measured immediately before next dosing; Area under the curve of plasma concentration per infusion; Mean concentration per infusion; Terminal phase half-life	0h, 2h, 6h, 12h, 14h (only cohort 1), 24h, 26h (only cohort 2 and 3), 48h, 72h, 74h (only cohort 3), days 5, 8, 13, 28	No
Primary	Assess the pharmacodynamic (PD) effects of CaCP29 on the change from baseline in plasma concentrations of C5a		0h, 2h, 6h, 12h, 14h (only cohort 1), 24h, 26h (only cohort 2 and 3), 48h, 72h, 74h (only cohort 3), days 5, 8, 13, 28	No
Primary	Safety variables will be summarized using descriptive statistics based on adverse event collection		28 days	Yes
Secondary	Anti-drug antibodies (ADA)	The development of ADA will be described by: Number of patients with detection of anti-drug antibody (ADA); Number of patients with detection of ADA at each time point measured	28 days or hospital discharge	No
Secondary	All-cause mortality rate		28 days	No
Secondary	Morbidity	Mean SOFA until Day 10; Modified mean SOFA until day 10 (calculated by omitting the Central Nervous System sub-score and calculating the renal subscore without taking urine output into consideration); Mean SOFA Sub-scores until Day 10; Days on ICU until Day 28; Number of patients ventilated until Day 14; Ventilator-free days until Day 14; Numbers of patients with renal replacement therapy (RRT) until Day 14; RRT-free days until Day 14; Numbers of patients with administration of vasopressor until Day 14; Vasopressor-free days until Day 14; Days without antimicrobial therapy (AMT) until Day 14	daily	No
Secondary	Fluid balance	Mean daily total fluid intake until Day 28 (maximal until ICU discharge); Mean daily total fluid output until Day 28 (maximal until ICU discharge); Mean daily fluid balance until Day 28 (maximal until ICU discharge)	28 days or ICU discharge	No
Secondary	Change in routine laboratory parameters as compared to baseline		Days 1, 2, 3, 4, 5, 8, 13, 28	Yes
Secondary	Change in ECG as compared to baseline		Days 2, 4, 8, 28	Yes
Secondary	Change in vital signs as compared to baseline		Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, Day 28	Yes